Durvalumab + Chemotherapy for Mesothelioma

(DREAM3R Trial)

No longer recruiting at 57 trial locations
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AL
DR
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Overseen ByStephanie Winata- International Sites
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
Prior Safety DataThis treatment has passed at least one previous human trial
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding durvalumab, an immunotherapy, to standard chemotherapy can benefit people with pleural mesothelioma, a cancer affecting the lung lining. The study aims to determine if this combination improves overall survival compared to other standard treatments or a different immunotherapy combo. It seeks participants with pleural mesothelioma that cannot be surgically removed. Those diagnosed with this condition and meeting the criteria might be suitable for the trial. As a Phase 3 trial, it represents the final step before FDA approval, offering access to potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroids or other immunosuppressive medications, you may need to stop them at least 28 days before starting the trial treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining durvalumab with chemotherapy is generally safe for people with certain cancers, such as mesothelioma. Studies have found that this combination is usually well-tolerated, with side effects similar to standard chemotherapy.

Other studies have found the combination of ipilimumab and nivolumab to be mostly safe for people with mesothelioma. Some patients lived longer, although results can vary.

Both treatment options have undergone testing in many patients, demonstrating general safety, though individual experiences may differ. Clinical trial participants receive close monitoring to manage any potential side effects.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Durvalumab with chemotherapy for mesothelioma because it introduces an innovative approach to treatment by leveraging the power of immunotherapy. Durvalumab is an immune checkpoint inhibitor that works by unleashing the immune system to attack cancer cells more effectively, a departure from traditional chemotherapy that directly targets and kills cancer cells. This combination aims to enhance the body's natural defenses, potentially leading to more durable responses and improved survival rates compared to conventional treatments alone. Additionally, the use of Ipilimumab and Nivolumab, both of which are also immune checkpoint inhibitors, presents an alternative approach by combining two immunotherapies to potentially provide a robust defense against cancer progression.

What evidence suggests that this trial's treatments could be effective for pleural mesothelioma?

Research has shown that combining durvalumab with chemotherapy, which participants in this trial may receive, may help treat advanced pleural mesothelioma. Studies have found that this combination can extend patients' lives and delay disease progression. More patients also experienced tumor shrinkage with this treatment.

For another treatment arm in this trial, the combination of ipilimumab and nivolumab, research indicates that some patients lived about 15.5 months on average. About one-third of these patients experienced a significant reduction in tumor size. Both treatments offer potential benefits for those facing this challenging condition.23467

Who Is on the Research Team?

PF

Patrick Forde, MD

Principal Investigator

Johns Hopkins University

AN

Anna Nowak, MD

Principal Investigator

Faculty of Health and Medical Sciences University of Western Australia

Are You a Good Fit for This Trial?

Adults over 18 with epithelioid pleural mesothelioma that can't be removed by surgery. They should have a good performance status, weigh more than 30 kg, and have acceptable blood test results. Women must not be pregnant and use contraception; men also need to follow certain contraceptive guidelines.

Inclusion Criteria

Life expectancy of at least 12 weeks.
Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments.
I am an adult diagnosed with a type of cancer called epithelioid pleural mesothelioma that cannot be removed by surgery.
See 8 more

Exclusion Criteria

My diagnosis was confirmed with a fine needle biopsy.
I have hearing loss or nerve issues that prevent me from taking certain medications.
I do not have active brain cancer symptoms or uncontrolled brain metastases.
See 17 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive durvalumab with standard chemotherapy or physician's choice of treatment for 4 to 6 cycles

12-18 weeks
Every 3 weeks

Maintenance

Participants in the experimental arm receive durvalumab every 4 weeks until disease progression, unacceptable toxicity, or withdrawal

Until disease progression
Every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months
Every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • Durvalumab
  • Ipilimumab and Nivolumab
  • Standard Chemotherapy
Trial Overview The trial is testing if adding durvalumab (an immunotherapy drug) to standard chemotherapy improves survival in patients with advanced pleural mesothelioma compared to standard chemotherapy alone or combined with other immunotherapies like ipilimumab and nivolumab.
How Is the Trial Designed?
3Treatment groups
Experimental Treatment
Active Control
Group I: Experimental Arm: Durvalumab + Chemotherapy, then Durvalumab MaintenanceExperimental Treatment1 Intervention
Group II: Control Arm: Chemotherapy, then ObservationActive Control1 Intervention
Group III: Control Arm: Ipilimumab and NivolumabActive Control1 Intervention

Durvalumab is already approved in European Union, United States, Japan for the following indications:

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Approved in European Union as Imfinzi for:
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Approved in United States as Imfinzi for:
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Approved in Japan as Imfinzi for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

PrECOG, LLC.

Lead Sponsor

Trials
19
Recruited
8,000+

Thoracic Oncology Group Australasia (TOGA)

Collaborator

Trials
1
Recruited
210+

University of Sydney

Collaborator

Trials
208
Recruited
417,000+

AstraZeneca

Industry Sponsor

Trials
4,491
Recruited
290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

The phase 2 PrE0505 trial demonstrated that the combination of the anti-PD-L1 antibody durvalumab with platinum-pemetrexed chemotherapy significantly improved overall survival in patients with unresectable pleural mesothelioma, achieving a median survival of 20.4 months compared to 12.1 months with historical controls.
The treatment was generally safe, with adverse events consistent with chemotherapy and no severe immunotherapy-related side effects, while genomic analyses suggested that a higher mutation burden and diverse T cell repertoire were associated with better clinical outcomes.
Durvalumab with platinum-pemetrexed for unresectable pleural mesothelioma: survival, genomic and immunologic analyses from the phase 2 PrE0505 trial.Forde, PM., Anagnostou, V., Sun, Z., et al.[2022]
Nivolumab (Opdivo) combined with ipilimumab (Yervoy) has been approved by the FDA as a first-line treatment for adults with unresectable malignant pleural mesothelioma, based on promising results from the CHECKMATE 743 trial.
The approval was supported by an interim analysis comparing the combination therapy to standard chemotherapy, indicating that this new treatment option may offer better outcomes for patients with this challenging cancer.
FDA Approves Nivolumab Plus Ipilimumab for Previously Untreated Unresectable Malignant Pleural Mesothelioma.Wright, K.[2021]
Durvalumab, a PD-L1 inhibitor, has been shown to be safe for patients with various solid tumors, with common side effects including pruritus and fatigue, based on a meta-analysis of 17 studies involving 1,529 patients.
Higher levels of PD-L1 expression in tumors are linked to better treatment responses to durvalumab, indicating that PD-L1 could serve as a useful biomarker for predicting the drug's efficacy.
Safety and efficacy of durvalumab (MEDI4736) in various solid tumors.Yang, H., Shen, K., Zhu, C., et al.[2022]

Citations

Durvalumab Plus Chemo Yields Inconclusive Results in ...Durvalumab with chemotherapy improved overall survival, progression-free survival, and objective response rates in advanced pleural mesothelioma ...
ESMO 2025: Primary results of DREAM3R: DuRvalumab ...LBA104 - Primary results of DREAM3R: DuRvalumab (MEDI4736) with chEmotherapy as first line treAtment in advanced pleural Mesothelioma - A phase 3 Randomised ...
Imfinzi With Chemo Produces Inconclusive Outcomes in ...Imfinzi plus chemotherapy improved overall survival, progression-free survival, and objective response rates in advanced pleural mesothelioma ...
Phase II MEDI4736 in Combination With Chemotherapy for ...Patients with pleural mesothelioma that can not be surgically removed will receive durvalumab, in combination with standard chemotherapy of pemetrexed and ...
Safety and efficacy of durvalumab (MEDI4736) in various ...Here, we report a meta-analysis investigating the safety and efficacy of durvalumab (MEDI4736), an inhibitor of PD-L1, in various solid tumors.
Study Details | NCT02899195 | Phase II MEDI4736 in ...Patients with pleural mesothelioma that can not be surgically removed will receive durvalumab, in combination with standard chemotherapy of pemetrexed and ...
Tremelimumab and durvalumab (MEDI4736) combination ...Tremelimumab in combination with durvalumab in first or second-line mesothelioma patients: Safety analysis from the phase II NIBIT-MESO-1 study.
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